Pavonia Cav. SPECIES (MALVACEAE SENSU LATO) AS SOURCE OF NEW DRUGS: A REVIEW

Abstract

Pavonia Cav., is a genus in the Malvaceae sensu lato family, containing 271 species with worldwide distribution, although with a higher diversity in America and Asia. Species from this genus are traditionally used in folk medicine with several biological activities, arousing scientific interest on the search for the substances responsible for such activities. This review aimed to provide and expand the scientific interest through phytochemical and pharmacological studies and the utilization of those plants in folk medicine. Species P. odorata and P. zeylanica are described in literature, specially at India, following the traditional medicine system Ayuverda, while the other species are studied mostly at Africa and America. There have been around 169 compounds isolated and characterized for such genus, most of them from the metabolic classes fat acids, terpenoids, flavonoids and phenolic compounds. Those species have shown in vivo, in vitro and in silico significant pharmacological activities, which include anti-inflammatory, analgesic, antimicrobial, cytotoxic, antitumoral, antidiabetic and antioxidant properties. Based on those informations, the search for new sources of plant based biologic prototypes with potential for the treatment of several diseases is of major scientific, economical and medicinal interest.

Keywords:
Pavonia Cav.; ethnopharmacological relevance; natural products; biological studies.

INTRODUCTION

Medicinal plants constitute the main therapeutic source of folk medicine. Traditional knowledges are passed through generations due to the stark believes that come since primitive folks and healers. Previous ethno-pharmaceutical-botanical studies form the foundation to the development of new drugs from medicinal herbs.¹

Plants provide an essential economic role as they are used as a drug source.² This fact rises in developing countries due to lesser side effects and easy access that low-income populations have to those plants, making them an almost inexhaustible source of remedies for those people.³

Several chemical compounds that act as potential therapeutic agents have been isolated from plant species.⁴ Studies about those compounds are based on ethnobotanical, chemical and pharmacological knowledges, aiming to find out new bioactive molecules. On this context, species from Malvaceae sensu lato family arouse major interests of the scientific community due to the fact that those species are important economic sources in agriculture, decorations, manufacturing, food and medicine.⁵

Among several genus belonging to Malvaceae sensu lato, we highlight Pavonia Cav., which has several biological and pharmacological activities described in literature about folk medicine. Those activities have been confirmed through the isolation, identification and characterization of secondary metabolites, as well as several pharmacological activities described for those compounds.⁶

The genus Pavonia Cav. includes approximately 271 species distributed worldwide, being more diverse in America and Africa, with only two species being recorded for Asia. A lot of chemical and pharmacological studies with species P. odorata and P. zeylanica are described in literature, mostly for India, due to the traditional medicine system Ayuverda.⁷

Approximately 224 species can be found in America, ranging from USA to Uruguay, including the Antilles and excluding Chile. In Africa, approximately 46 species can be found.⁸ In Brazil, 136 species of Pavonia can be found, ranging from Amazon rainforest, Caatinga, Cerrado, Atlantic Forest, Pampas and Pantanal wetlands.⁹

Based on presented data, this review aims to accomplish a bibliographical survey about traditional uses of Pavonia species and evaluate the chemical and pharmacological potential of this genus in order to drive future researches based on natural products as a source of new drugs.

METHODOLOGY

Information about the use of plants by folk medicine, phytochemical studies, botanic characteristics and pharmacological activities of genus Pavonia have been based and collected from scientific data banks such as: ‘Web of Science’, ‘Scifinder’, ‘Pubmed’ and ‘Scholar Google’, using papers, books, dissertation and thesis from the year 1918 until April 2021 and searching for the keyword ‘Pavonia’. Following this methodology, we consulted 156 scientific articles, having, as inclusion criteria, the presence of information regarding the use of Pavonia genus in traditional medicine, phytochemical studies, pharmacological and/or biological activities. The exclusion criteria of the articles involved repetition of those in different databases, review articles that contained references used in the manuscript, information with the keyword ‘Pavonia’ that do not concerns the genus, articles with only botanical data or articles not available for access on the platforms used. A single patent referring to the species P. schiedeana (JP 2001181172A (2001)) was found as part of a cosmetic composition.

The development of this revision paper aimed the study of this genus in order to expand the scientific interest through knowledge of isolated compounds with several biological activities, as those are the candidates to new drugs isolated from Pavonia species.

The present study and data have been extracted by the author (JBLA) and confirmed by other (DAF, CMS, PIVS, MFVS). All data are resumed in tables and their descriptions have been resumed as updated information.

RESULTS AND DISCUSSION

Botanical description

Pavonia comprises species of herbs, shrubs and bushes. Its flowers are, generally, solitary, composed by four epicalyxes, several free bracteoles, a tubulous and cupuliform calyx composed by five petals, carpels uniovulate and stigma capitate (Figure 1). The fruits are schizocarp, formed by five mericarps with a nervous-reticulate dorsal face, smooth lateral faces and smooth or striated obovoid or reniform seeds.¹⁰

Figure 1
Pavonia plants. A) P. alnifolia, B) P. multiflora, C) P. fruticosa, D) P. malacophylla, E) P. hastata, F) P. varians, G) P. procumbens, H) P. urens, I) P. odorata, J) P. spinifex

Some species of Pavonia possess floral nectaries formed by multicellular glandular trichomes, providing a thick area located near the internal base of calyx. This characteristic attracts hummingbirds, which are pollinators of tubulous flowers, such as P. glazioviana¹¹ and P. multiflora. Species that possesses flowers with twisted corolla and short staminal tube formed by free stamens, such as P. malacophylla, P. varians, P. zeylanica and P. distinguenda, are pollinated by bees.¹²

Ethnopharmacological relevance

Different species of Pavonia Cav. are related in folk medicine as a treatment for several diseases. Among the most used parts of those plants used by some tribes in therapeutics are flowers, bark, roots, rhizomes and flowers (Table 1).

Table 1
Species of Pavonia genus and their uses in folk medicine

Scientific name/ Popular name	Used plant part	Traditional Use	Therapeutic Properties	References
Pavonia cancellata/Malva-rasteira	LV	Poultice	Boils	31
Pavonia distinguenda	AP	*	Antitumor and antibacterial	32
Pavonia fruticosa/Anamu	WP	Decoction	Antipyretic and common cold	33
Pavonia lasiopetala/Pavonia rosa	LV	*	Breaks and disintegrates kidney and urinary stones; Diuretic	34
Pavonia odorata/Sugandhibala	RH	*	Dysentery, anti-inflammatory, anti-hemorrhagic; Antipyretic, digestive and astringent	35,36
	RH and LV	*	Antipyretic, stomachic, dysentery and antiurolytic	37,38
	WP	*	Antipyretic, stomachic, dysentery; Rheumatism; Antiemetic; Anti-hemorrhagic; Demulcent, carminative, diaphoretic, diuretic, anti-inflammatory, spasmolytic and astringent	29,39-45
	ST and RT	*	Antipyretic	7
	ST	*	Bone fractures	46
	AP	*	Colds, diaphoretic, diuretic, demulcent; Antipyretic, anti-inflammatory and anti-hemorrhagic	47-49
	*	*	Antipyretic, stomachic, dysentery; Anti-hemorrhagic; Skin diseases, anti-inflammatory, spasmolytic; Nervous weakness	3,50-54
	LV	Leaf juice	Dysentery; Gonorrhea; Anti-halitosis	12-15
		Paste	Rheumatism; Foot infection, and antipyretic	16,17
	RT	*	Stomachache, anti-inflammatory, anti-hemorrhagic; Antipyretic, diuretic; Carminative, diaphoretic, polydipsia, burning when urinating, demulcent astringent, stomachic, haemorrhages from intestines; bleeding disorders, dysentery and antiulcerogenic; appetizer	4,29,52,55-58
		Paste	Athlete’s foot	1,59
		Powder	Dislocations of bone joints; Osteoarthritis	21,22
		Decoction	Dysentery and carminative	60,61
Pavonia procumbens	*	*	Antiulcerogenic, fumigation, vermifuge, analgesic and skin infections	2,51,62-64
Pavonia schiedeana/Cadillo	RT	Decoction	Retained placenta and prevention of miscarriage	65
	RT and WP	Poultice	Antipyretic	66
	LV	Infusion	Hypoglycemic; retained placenta and prevention of miscarriage	65,67
Pavonia senegalensis	LV	Aqueous extract	Bone and soft tissue infections	68,69
	RT	Inhalation and infusion	Diarrhea and induce labour	70,71
	SD	Powder	Contraceptive	18
Pavonia spinifex	FL	Infusion	Analgesic and skin problems	72,73
	LV and TW	Infusion	Stomach problems, gallstones and liver pain
	LV	*	Hepatoprotection, antioxidant, anticancer, antifungal and antibacterial	74
Pavonia urens	AP	Inhalation and decoction	Antipyretic	75
	RT	*	Pneumonia and stomachic	76,77
		Decoction	Toothache	19,20
	LV	*	Boils	78
		Smoke	Repellent for mosquitoes and house flies	79-81
Pavonia varians/ Malva-peluda	*	*	Infections of the digestive system, and anti-inflammatory	82
Pavonia xanthogloea/ Erva-de-ovelha	*	*	Antimicrobial and antitumor	83,84
Pavonia zeylanica/ Citramutti	LV	*	Eczema; Eye diseases; Antipyretic, Anthelmintic, anti-inflammatory, analgesic, toothache; Dysentery, anti-hemorrhagic and emollient	43,85-91
		Decoction	Cough with phlegm	23
		Ground	Constipation in animals	92
		Paste	Bone fractures; Healing of acute and chronic wounds	24,25
	*	*	Skin diseases, anthelmintic, leprosy, scabies, ringworm, dermatitis, acne, wounds and antiulcerogenic; Blood circulation	3,93
Pavonia zeylanica/ Citramutti	WP	Inhalation	Wound dressing	94
		*	Antipyretic and anthelmintic; Paralysis; Joint pain	4,95,96
		Infusion and leaf juice	Vermifuge and purgative	26-29
	RT	*	Demulcent, carminative, diaphoretic, diuretic, astringent, tonic, anti-hemorrhagic and anti-inflammatory; Antiulcerogenic	88,97
		Powder	Dislocations of bone joints; Osteoarthritis	21,22

^*APFLFRLVRHRTSDSTTWWP

Juice of P. odorata leaves is used by traditional medicine Ayuverda as a treatment for dysentery, gonorrhea and halitosis, whereas leaves macerate as a paste are used as a treatment for rheumatism, foot infections and antipyretic.¹³-¹⁸

Powder from seeds of P. senegalensis is used as a contraceptive.¹⁹ Decoct of P. urens roots is largely used as a treatment for toothache.²⁰,²¹ Brewing of roots and leaves of P. zeylanica, as well as decocts, powder and pastes are largely used by eastern communities as a treatment for osteoarthritis, joint pain, bone fractures, cough with discharge and healing of wounds.²²-²⁶ Leaves’ juice and the entire plant prepared as infusion are also used for its vermifuge and purgative properties.²⁷-³⁰

Several ethnopharmacological studies regarding Pavonia species have been described in literature, which give us basis for deepening the chemical and pharmacological knowledge of those herbs, since many of the pharmacological activities are related to traditional use of medicinal plants, therefore providing essential information to the development of new drugs.

Chemical composition

Based on literature data, 29 references in the area of phytochemistry have been find to species of the genus Pavonia: 10 papers referred to species P. odorata (06) and P. zeylanica (04); 9 papers referred to species P. malacophyla (03), P. glazioviana (03) and P. sepium (03), and; 2 papers referred to P. cancelatta. Besides, several other papers have been related in this field with the species P. varians, P. xanthogloea, P. sepioides, P. distinguenda, P. multiflora, P. hastata, P. lasiopetala, P. schiedeana and P. alnifolia. 169 compounds have been isolated and/or identified in the genus Pavonia (Table 2), comprehending the most diverse classes of secondary metabolites ever related.

Table 2
Isolated compounds from Pavonia genus

Nº	Name	Source	Reference
Fatty acids
1	Malvalic acid	SD of P.sepiu. and P.z.	98-101
2	Sterculic acid
3	Palmitic acid	SD of P.z., RT and AP of P.o.	48,101-105
4	Stearic acid
5	Oleic acid
6	Linoleic acid
7	Dihydrosterculic acid	SD of P.z.	101
8	(9Z,12Z,15Z)-9,12,15-Octadecatrienoic acid 2,3-bis(trimethylsilyloxy)propyl-ester	RT of P.o.	48,102-104,106
9	Isovaleric acid
10	Caproic acid
11	Dodecanoic acid	AP of P.o.	105
12	Methyl tetradecanoate
13	Tetradecanoic acid
14	Methyl-(2E,6E)-farnesate
15	Pentadecanoic acid
16	Methyl palmitate
17	Methyl linoleate
18	Methyl oleate
Terpenoids
19	α-amirine	AP of P.mal.	107
20	β-amirine
21	Lupeol	AP of P.mal. and P.d.	31-108
22	Blumenol C	LV of P.mul.	109
23	Vomifoliol
24	4,5-dihydroblumenol A
25	3-oxo-α-ionol
26	Loliolide
27	Taraxerol p-methoxybenzoate
28	Cycloart-23Z-en-3β, 25-diol	AP of P.g.	110
29	Cycloart-25Z-en-3β, 24-diol
30	Taraxerol	AP of P.d.	31
31	Germanicol
32	Cedran-diol,8S,13	RT of P.o.	48,102-104,106
33	Cedrol
34	S-guaiazulene
35	Pinocarveol
36	α-terpinene
37	Pavonenol*
38	β-pinene
39	p-cymene
40	1,8-cineole	AP of P.o.	105
41	(Z)-linalooloxide
42	(E)-linalooloxide
43	Linalool
44	(E)-pinocarveol
45	Borneol
46	Menthol
47	Terpinen-4-ol
48	p-cymen-8-ol
49	α-terpineol
50	Carvone
51	Geraniol
52	Thymol
53	Eugenol
54	β-damascenone
55	β-caryophyllene
56	β-eudesmol
57	Muurolane
58	Farnesyl acetone
59	Phytol
60	β-caryophyllene oxide
61	Guaiol
62	γ-eudesmol
63	α-eudesmol	RT and AP of P.o.	48,102-105
64	α-pinene
Steroids
65	Sitosterol-3-O-β-D-glucopyranoside	AP of P.c., P.mal. and P.g.	107,110-112
66	Stigmasterol-3-O-β-D-glucopyranoside
67	β-sitosterol	AP of P.c., P.mal. and P.d.; RT of P.o.	31,106, 107,111, 112
68	Stigmasterol	AP of P.c.	111-112
69	Ethyl iso-allocholate	RT of P.o.	106
Flavonoids
70	Kaempferol 3-O-(6’’-O-p-coumaroyl glucoside (Tiliroside)	AP of P.c., P.x., P.mal., P.v., P.g., P.d.	11,31,83, 107, 111-114
71	3,7-di-O-methylkaempferol	AP of P.c.	111-112
72	Quercetin	FL of P.h. and P.l.; AP of P.x., P.mal., P.g.	11,83, 107-115
73	2-(3,4-dihydroxyphenyl)chromane-3,5,7-triol (Cyanidin)
74	Rutin	AP of P.a. and P.x.	83-116
75	Quercitrin	AP of P.x.	83
76	Kaempferol	AP of P.mal., P.g.	11-107
77	5,8-dihydroxy-7,4’-dimethoxyflavone	AP of P.mal.	108
78	5,7-dihydroxy-4′-methoxyflavone (Acacetin)	AP of P.g.	11,110, 117
79	5,7-dihydroxy-3,8,4’-trimethoxyflavone
80	5-hydroxy-3,7,8,4’-tetramethoxyflavone
81	5,7,4’-trihydroxy-3,8-dimethoxyflavone
82	5,7,4’-trihydroxy-3-methoxyflavone
83	Kaempferol-3-glucoside (Astragalin)	AP of P.d.	31
84	Dihydrokaempferol (Aromadendrin)	RT of P.o.	48,102-104
85	Aromadendrene
Compounds Phenolics
86	Gossypol	SD of P.sch.	118
87	Gallic acid	AP of P.x.	83
88	Catechin
89	Chlorogenic acid
90	Caffeic acid	AP of P.x.; LV of P.sepio.	83-119
91	Vanillic acid	LV of P.mul. and P.sepio.	109-119
92	Ferulic acid
93	p-Hydroxybenzoic acid
94	p-coumaric acid	LV of P.mul.	109
95	Salicylic acid	LV of P.sepio.	119
96	Cinnamic acid
97	p-Hydroxyphenylacetic acid
98	Gentisic acid
99	4-[(1E)-prop-1-en-1-yl]benzoic acid
100	2-[(1E)-prop-1-en-1-yl]benzoic acid	LV of P.sepio.	119
101	3-[(1E)-prop-1-en-1-yl]benzoic acid
102	Syringic acid
103	Protocatechuic acid
Other compounds
104	173-ethoxy-phaeophorbide a	AP of P.mal.	107-108
105	Phaeophytin b
106	132-S-hydroxy- phaeophytin a	AP of P.g. and P.mal.	110
107	132-S-hydroxy-173-ethoxy-phaeophorbide a
108	Triacontanol
109	cis-p-coumaric acid ethyl ester
110	Pavophylline	ST of P.z.	26-120
111	Methyl-19-ketotetracosanoate
112	12-Methyl-tetracosan-9-one	FL of P.z.	121
113	Phenyl-alcohol	RT of P.o.	48,102-104,106
114	Benzoic acid-2-hydroxy-ethyl-ester
115	5aH-3a,12-methano-1H-cyclopropa [5’,6’]cyclodeca[1’,2’,1,5] cyclopenta [1,2-d] [1,3]dioxal-13-one
116	2,7-diphenyl-1,6 dioxopyridazino[4,5,2’,3’] pyrrolo[4’,5’-d]pyridazine
117	Bicyclo [4, 3, 0] nonan-7-one,1-(2-methoxyvinyl)
118	1,5-bis (3-cyclopentyl­propoxy)-1, 13,3,5,5-hexa­methyltrisiloxane
119	Pavonene*
120	Isovaleraldehyde
121	Azulene
122	Hexahydrofarnesyl-acetone	RT and AP of P.o.	48,102-105
123	6-methyl-5-hepten-2-one
124	Isopentyl alcohol	AP of P.o.	105
125	Pentanol
126	Hexanol
127	Benzyl alcohol
128	Phenylethyl alcohol
129	2-methoxy-p-cresol
130	2-methoxy-4-vinylphenol
131	2,4-bis(1,1-dimethyethyl)-phenol
132	Acetophenone
133	2-nonanone
134	Isophorone
135	4-keto-isophorone
136	p-menth-4-en-3-one
137	Dihydro-5-pentyl-2-(3H)-furanone	AP of P.o.	105
138	Hexahydropseudoionone
139	α-ionone
140	Dihydro-β-ionone
141	Dihydropseudoionone
142	β-ionone
143	4,8,12-trimethyltridecan-4-olide
144	Phthalic acid
145	2-pentyl-furan
146	3-butyl-pyridine
147	p-allyl-anisole
148	3-phenylpyridine
149	Dihydroactinolide
150	Ageratochromene
151	Hexadecanolactone
152	Hexanal
153	Benzaldehyde
154	Phenylacetaldehyde
155	(2E)-nonen-1-al
156	1,3,4-trimethyl-3-cyclohexene-1-carboxyaldehyde	AP of P.o.	105
157	2-methyl-3-phenyl-propanal
158	2-hydroxy-4-methoxy-benzaldehyde
159	Pentadecanal
160	p-ethoxy-ethyl-benzoate
161	Isobutyl-phthalate
162	Naphthalene
163	Dodecane
164	2-methyl-naphthalene
165	Tetradecane
166	2,3,6-trimethyl-naphthalene
167	3-(2-methyl-propenyl)-1H-indene
168	γ-cadinene
169	Hexadecane

P.a.P. alnifoliaP.c.P.cancellataP.d.P.distinguendaP.g.P.glaziovianaP.h.P.hastataP.l.P.lasiopetalaP.mal.P.malacophylla.P.mul.P.multifloraP.o.P.odorataP.sch.P.schiedeanaP.sepio.P.sepioidesP.sepiu.P.sepiumP.v.P.variansP.x.P.xanthogloeaP.z.P.zeylanicaAPFLLVSDSTRT^*

Fat acids, terpenoids, steroids, flavonoids, phenolics and other compounds such as pheophytins, hydrocarbons and volatile oils are some of the substances that can be found in the genus Pavonia. A broad profile of such compounds within has been detected in a study of the chemical composition of oils in the aerial parts of the species Pavonia odorata through hyphenated gas chromatography techniques coupled with mass spectrometry.¹⁰⁵ All compounds and their chemical structures are related in Table 2 and Figure 2, respectively.

Figure 2
Compounds isolated from Pavonia species

Fatty acids

Fatty acids are molecule that consists of the most diverse lipids and, by enzymatic action, become free fatty acids, presenting powerful biological activities.¹²²

Studies described in literature review that activities of those compounds depend on the level of unsaturation and the size of hydrocarbons chain, resulting antibacterial, antifungal and antimycobacterial activities.¹²³,¹²⁴ A recent study has shown that P. malacophylla and P. cancellata have palmitic, oleic and linoleic acids as majoritarian fatty acids.¹²⁵

Eighteen fatty acids have been isolated and identified in species P. sepium, P. odorata and P. zeylanica (Table 2). Palmitic (3) and caproic (10) fatty acids showed significant activities in preparatory in silico studies as having inhibitory properties for the activities of glycerol-kinase enzyme from the fungus Epidermophyton floccosum¹⁰⁴ and inhibitory properties for the alcohol-dehydrogenase enzyme from the protozoan Entamoeba histolytica.⁵³

Terpenoids and steroids

Terpenoids can be find in several groups of organisms. In plants, they are present under distinct aspects such as volatile molecules or adhered to resins. Their oxygenated, hydrogenated and dehydrogenated derivates have hydrocarbons as a base-structure, being widely distributed among plant species.¹²⁶

Forty-six terpenoids have been isolated and identified in P. odorata, P. multiflora, P. malacophylla, P. glazioviana and P. distinguenda, being the last one of the most common of Pavonia species. Terpenoids α-amirine (19) and β-amirine (20) showed in vitro antibacterial activities against Escherichia coli.¹⁰⁷ The terpenoid cicloart-23Z-en-3β-25-diol (28) also presented in vitro antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Candida tropicalis, Candida parapsilopsis e Aspergillus fumigatus.¹¹⁰

Compounds loliolide (26) and the taraxerol p-metoxybenzoate (27) have demonstrated significant in vitro activities on the inhibition of electrons flux in photosystem II of plants, therefore allowing those molecules to become future candidates to herbicides as they prevent photosynthesis.¹²⁷

Steroids are a minority class in Pavonia genus, with only five isolated compounds (65-69). Phytosteroids share as common structure ciclopentanoperidrofenaterne as carbonic skeleton, being β-sitosterol and stigmasterol the most common steroids of this genus and commonly encountered attached to sugar monomers.¹²⁸

Flavonoids and phenolic compounds

Flavonoids are the most important and diversified class of phenolic compounds among natural products, being relatively abundant secondary metabolites and responsible for several functions in plants’ organisms.¹²⁹

Seventeen flavonoids have been isolated from Pavonia species, being sixteen of those members of subclass flavone (70-84) and one, to flavanonol subclass (85). Many isolated flavonoids have glycosids attached to their structures.

Among the isolated compounds, flavonoid 5,7-dihydroxy-3,8,4’-trimethoxyflavone (79) has demonstrated in vitro antimicrobial, in silico anticancer, in vitro antineoplasic, in vitro antiprotozoal and in vito photoprotective activities.¹³⁰,¹³¹

The compound tiliroside (70) has demonstrated in vitro and in vivo antihypertensive activities, leading to reduction of peripheric vascular and vasorelaxant resistances by blocking the Calcium channels dependent of voltage (Ca_V) in cells of vascular smooth muscle (VSMCs);¹³² in vitro antimicrobial activity;³¹,¹⁰⁷ in silico antidiabetic activity through interaction with human pancreatic α-amylase enzyme;¹¹⁴ in vitro anticancer and anticolinesterasic activities.³¹

Nineteen phenolic compounds (87-105) have been identified and isolated from the species P. xanthogloea, P. sepioides, P. multiflora and P. schiedeana. Studies demonstrated that those compounds presented different activities. Gross ethanolic extract and fractions of ethyl acetated from extractive process of P. sepioides leaves have shown a large quantity of phenolic compounds present on the samples, which explains the antioxidant activity of those substances against free radicals inhibitions tests through the methods of DPPH and ABTS.¹¹⁹

Besides that species, other studies have shown a large potential of antioxidant activity as a primordial activity of those phenolic compounds such as described for P. xanthogloea, P. zeylanica, P. odorata, P. distinguenda, P. varians, P. glazioviana and P. procumbens.³¹,⁴⁴,⁸²,⁸³,⁹⁰,¹⁰⁵,¹¹⁷,¹³³-¹³⁵

Other compounds

Differently from previously mentioned compounds, other classes of secondary metabolites have been isolated and identified in a lesser frequency on Pavonia species. Among those compounds, we can list alcohols, aldehydes, ketones, pheophytins and hydrocarbons (106 171) (Table 2, Figure 2).

Chaves¹⁰⁷ has conducted a phytochemical study of P. malacophylla, isolating and identifying the compound 17³-ethoxy-phaeophorbide A (104), which has presented in vitro antibacterial activity against Staphylococcus aureus and Escherichia coli.

Pharmacological study

Several pharmacological activities involving Pavonia species have been arousing interest of scientific community hence there is a large collection of reports of their use in folk medicine. Researches have been developed to confirm the anti-inflammatory, analgesic, antioxidant, cytotoxic, antitumoral, antidiabetic, antimicrobial and antiviral potential of Pavonia species through scientific analysis (Table 3).

Table 3
In vitro, in vivo, and in silico biological studies reported from Pavonia genus

Species	Material used	Experimental model	Reference
Anti-inflammatory and Analgesic Activity
P.z.	Leaves alcoholic extract	In vitro - anti-inflammatory and antinociceptive by inhibition the arachidonic acid pathway	88
P.z.	Leaves and stems aqueous extract	In vitro - anti-inflammatory and analgesic	136
P.z.	Leaves ethanolic extract	In vitro - anti-inflammatory activity by inhibition protein denaturation	90
P.o.	Roots extract	Anti-inflammatory activity	137
P.o.	Roots methanolic, chloroform and ethyl acetate extract	In vitro - anti-inflammatory	106
Antioxidant Activity
P.x.	Aerial parts hexane fractions, dichloromethane, ethyl acetate, n-butanol, and water ethanolic extract	In vitro - inhibition of DPPH, H2O2 and sodium nitroprusside radicals (SNP)	83
P.v.	Aerial parts hydroalcoholic extract	In vitro - stabilization of radicals free DPPH	82
P.gla.	Aerial parts ethanolic extract	In vitro - inhibition of DPPH radicals	117-134
P.pro.	Leaves methanolic extract	In vitro - inhibition of ABTS radicals	135
P.d.	Aerial parts methanolic extract and hexane fraction	In vitro - inhibition of DPPH radicals	31
P.sep.	Leaves ethanolic extract, hexane fraction, dichloromethane fraction, ethyl acetate fraction and aqueous fraction	In vitro - inhibition of DPPH and ABTS radicals	119
P.z.	Leaves ethanolic extract	In vitro - inhibition of radicals free	90
P.o.	Whole plant methanolic extract, hydroalcoholic fractions and ethyl acetate	In vivo - inhibition of lipoperoxidation	44
P.o.	Aerial parts essencial oils	In vitro - inhibition of ORAC radicals	105
P.o.	Leaves aqueous extract	In vitro - inhibition of FRAP, NO radicals and reduction of phosphomolybdenum	133
Antitumor and Cytotoxic Activity
P.gla.	5,7-dihydroxy-3,8,4’-trimethoxy flavone	In silico - uterine and ovarian anticancer; In vitro - antineoplastic activity against sarcoma, carcinoma, melanoma and squamous cells	130-131
P.d.	Methanolic extract	In vitro - anticancer activity against leukemia, ovary, colon, prostate, kidney, breast, resistant breast, lung and melanoma; cytotoxic for Artemia salina larvae	31
	Hexane fraction
	Dichloromethane fraction
	Tiliroside
P.o.	Whole plant methanolic extract, hydroalcoholic and ethyl acetate fractions	In vitro - Erlich’s ascites carcinoma (EAC) and cytotoxic	44
P.o.	Whole plant methanolic extract	In vitro - lung and human breast cancers	138
Antidiabetic Activity
P.v.	Tiliroside	In silico - interaction by the human pancreatic α-amylase enzyme	114
P.z.	Leaves aqueous extract	In vitro - reduced blood sugar levels	86-136
	Leaves and stems aqueous extract
P.o.	Roots extract	In vitro - reduced blood sugar levels	139
Antimicrobial and Antiviral Activity
P.mal.	Mixture of α-amirine and β-amirine	In vitro - Staphylococcus aureus, Escherichia coli and Candida albicans	107
	173-ethoxy-pheoforbide A
	Tiliroside
	Acetate Fraction
	Hexane:Acetate (9:1) fraction
	Hexane:Acetate (1:1) fraction
	Acetate:Methanol (9:1) fraction
	Acetate:Methanol (1:1) fraction
	Aerial parts Crude Ethanolic Extract
P.gla.	5,7-dihydroxy-3,8,4’-trimethoxy flavone	In vitro - Escherichia coli, Pseudomonas aeruginosa, Candida tropicalis, Candida parapsilopsis, Aspergillus flavus and Aspergillus fumigatus	131
	Cicloart-23Z-en-3β, 25-diol
P.pro.	Leaves methanolic extract	In vitro - Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis	63
P.u.	Roots methanolic extract	In vitro - Candida albicans, Aspergillus fumigatus, Fusarium culmorum, Staphylococcus aureus, Pseudomonas syringae and Erwinia amylovora.	76-77
P.spi.	Whole plant ethanolic extract	In vitro - Staphylococcus aureus and Klebsiella pneumoniae	140
P.d.	Aerial parts methanolic extract, hexane, dichloromethane, ethyl acetate and n-butanolic fractions	In vitro - Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtillis, Klebsiela pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Salmonella setubal	31
	Tiliroside
P.z.	Leaves dichloromethane extract	In vitro - Escherichia coli and Klebsiella aerogenes	85
	Leaves ethyl acetate extract	In vitro - Escherichia coli
	Leaves diethyl ether extract	In vitro - Staphylococcus aureus
	Leaves methanolic extract	In vitro - Bacillus subtilis, Escherichia coli and Klebsiella aerogenes
P.o.	Rhizomes essential oil	In vitro - Staphylococcus aureus, Bacillus subtilis, Bacillus mycoides, Diplococcus pneumonia,Salmonella typhi H, Salmonella paratyphi A., Shigella flexneri, Vibrio cholerae Ogawa,Escherichia coli, Klebsiella sp.; Helminthosporium sp., Fusarium solani, Aspergillus flavus, Aspergillus niger, Aspergillus nidulans, Aspergillus fumigatus, Botrydiplodia sp., Alternaria sp., Rhizophus nodosus, Colletotrichum capsici, Trichophyton mentagrophytes, Chrysosporium indicum and Rhizoctonia sp.	35,141-143
P.o.	Roots methanolic, chloroform and ethyl acetate extracts	In vitro - Staphylococcus aureus and Candida albicans	106
P.o.	Caproic and palmitic acids	In silico - inhibition of the activity of the glycerol kinase enzyme of Epidermophyton floccosum	104
Other Activities
P.c.	Tiliroside	In vitro e in vivo - antihypertensive activity by reducing resistance peripheral vascular and vasorelaxing by blocking voltage-gated calcium channels (CaV) in vascular smooth muscle cells (VSMCs)	132
P.gle.	Leaves aqueous extract	In vitro - phytopesticidal activity against termites	144
P.l.	Leaves aqueous extract	In vitro - antiurolytic activity (inhibition of calcium oxalate nucleation by disintegrating into smaller particles with increasing fraction concentrations)	34
P.pra.	Leaves ethanolic extract	In vitro - inhibition of tyrosinase enzyme	145
P.sch.	Aerial parts methanolic extract	In vitro - Antiretroviral activity (reverse transcriptase inhibition)	146-147
P.sch.	Aqueous extract	Promoter of peripheral vascular blood flow; improves dryness and roughness of the skin and stimulates hair growth	148
P.sen.	Leaves aqueous ethanolic extracts	It does not present acute toxicity, however after 28 days the extract becomes nephrotoxic and slightly hepatotoxic	68
P.a.	Stems hydroethanolic extract	In vivo e in vitro - dose-dependent hypotensive and ACE inhibitor	116
P.a.	Stems ethanolic extract	In vivo - gastroprotective activity	149
P.mul.	Leaves ethanolic extract	In vitro - inhibitor of cathepsins K and V	109
P.mul.	Loliolide	In vitro - inhibition of electron flow in photosystem II	127
	Taraxerol p-methoxybenzoate
P.gla.	5,7-dihydroxy-3,8,4’-trimethoxy flavone	In vitro - antiprotozoan (Trichomonas vaginalis)	130-131
		In vitro - photoprotective activity with a high level of protection (25.01 FPS)
P.d.	Tiliroside	In vitro - inhibition of acetylcholinesterase (AChE) activity	31
P.z.	Leaves methanolic extract	In vitro - larvicide against Culex quinquefasciatus	150
P.z.	Leaves methanolic, hexanic, chloroformic, ethyl acetate and acetonic	In vitro - larvicide against Anopheles stephensi and Culex quinquefasciatus	151
P.z.	Leaves and stems ethanolic extract	In vitro - laxative activity	136
P.z.	Leaves ethanolic extract	In vitro - inhibition of denaturation of albumin, stabilization of the erythrocyte membrane and protection against hemolysis	90
P.o.	Rhizomes essential oil	In vitro - anthelmintic against tapeworms and roundworms	35,141-143
P.o.	Rhizomes essential oil	In vitro - Hypotensive, antispasmogenic and intestinal relaxant	36
P.o.	Whole plant extract	Antirheumatic, antiasthmatic/antibronchial activities	137
P.o.	Roots aqueous and alcoholic extracts	In vitro - anthelmintic against Pheretima postuma	152
P.o.	Leaves methanolic extract	In vitro - larvicidal and repellent activity against Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus	153
P.o.	Caproic, palmitic acids and hexahydropharnesyl-acetone	In silico - inhibition of the activity of the enzyme alcohol dehydrogenase of Entamoeba histolytica	53
P.o.	Whole plant aqueous extract	In vitro - inhibits the formation of minerals in urine samples	154
P.o.	Whole plant aqueous extract	In vitro - controls human urinary calculogenesis	155
P.o.	Whole plant extract	Antiparasitic activity against Entamoeba histolytica	29

P.a.P. alnifoliaP.c.P.cancellataP.d.P.distinguendaP.gla.P.glaziovianaP.gle.P.glechomifoliaP.l.P.lasiopetalaP.mal.P.malacophyllaP.mul.P.multifloraP.o.P.odorataP.pra.P.praemorsaP.pro.P.procumbensP.sch.P.schiedeanaP.sen.P.senegalensisP.sep.P.sepioides;P.spi.P.spinifex;P.u.P.urensP.v.P.variansP.x.P.xanthogloeaP.z.P.zeylanica

Anti-inflammatory and analgesic activities

Plants constitute a vast and precious source of natural products, which are essential to human health as they play several biological roles such as anti-inflammatory and analgesic activities, as it has been demonstrated by some studies over extracts and isolated compounds.¹⁰⁶

Alcoholic extract of P. zeylanica leaves has shown in vivo anti-inflammatory activity in rat foot edema induced by carrageenan and in vivo antinociceptive activity by inhibition of arachidonic acid formation.⁸⁸ Methanolic, chloroformic and ethyl acetate extracts of P. odorata roots have also demonstrated in vivo anti-inflammatory activity in albino rat foot edema induced by carrageenan.¹⁰⁶ (Table 3).

Antioxidant activity

Antioxidants are substances that control the action of free radicals, minimizing the risk of diseases, specially those related to oxidative damage on nervous system. Naturally, some enzymes are responsible for the protection of harmful effects of free radicals, such as catalasis and dismutasis superoxide, as well as natural products with antioxidant action such as ascorbic acid, tocopherol, phenolics and flavonoids.¹³³

The evaluation of antioxidant activity of extracts from the aerial parts of Pavonia species has shown the presence of phenolics and flavonoids as its constituents, having those compounds demonstrated a huge antioxidant potential in tests through the methods DPPH (1,1-diphenil-2-picril-hidrazil), H₂O₂ (hydrogen peroxide), NO (nitric oxide), ABTS (2,2’-azino-bis(3-etilbenzotiazoline-6-sulphonic) acid), FRAP (Ferric Reduction Antioxidant Power), SNP (Sodium Nitroprussiate radicals), phosphomolybdenium reduction, ORAC (Oxygen Radical Absorbance Capacity) and TBARS (Thiobarbituric Acid Reactive Substances) (Table 3).

Cytotoxic and anticancer activities

Cancer is one of the most lethal diseases that affects humankind. Some phytochemical studies have demonstrated anticancer potentials in several plants due to their chemoprotective and antioxidant properties, which make plants an option to minimize the adverse effects of conventional cancer treatments.¹⁵⁶

Extracts and isolated compounds from P. glazioviana, P. distinguenda and P. odorata have demonstrated anticancer activities. The tiliroside flavonoid isolated from P. distinguenda has shown in vitro anticancer activity against leukemic, ovarian, colon, prostate, kidney, breast, resistant breast and melanoma cells, besides being cytotoxic to Artemia salina larvae.³¹

Other flavonoid isolated from P. glazioviana (5,7-dihydroxy-3,8,4’-trimethoxyflavone) (79) has shown in silico anticancer activity against carcinogen uterine and ovarian cells, while having in vitro antineoplastic activity against sarcoma, carcinoma, melanoma and squamous cell carcinoma.¹³⁰,¹³¹

Extracts from the whole plant of P. odorata has shown in vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC), lung and breast cancer.⁴⁴,¹³⁸

Antidiabetics activity

Several plants are used by folk medicine worldwide against diabetes.⁸⁶ Some of the species quoted in literature are P. zeylanica and P. odorata. Extracts from their leaves, stems and roots have been evaluated regarding their in vitro antidiabetic activity, being constated a significant reduction of glycose levels in bloodstream.⁸⁶,¹³⁶,¹³⁹

In silico hypoglycemic activity of the tiliroside flavonoid isolated from P. varians through the interaction of this compound with human pancreatic α-amylase enzyme presented a lesser linking energy of -9.4 kcal/mol, being more stable in its active site when compared to the standard drug acarbose, that presented an energy of -7.6 kcal/mol.¹¹⁴

Antimicrobial activity

Bacterial resistance has been increasing significatively in the last years, which leads to high mortalities caused by generalized infections. This fact is a consequence of ungovernable use of antibiotics. For those reasons, the search for new natural compounds with antimicrobial activity and new action mechanisms if necessary for the control of such micro-organisms.¹⁴⁰

Extracts, fractions and compounds isolated from Pavonia species have shown a great antimicrobial potential that has already been described in literature. Among the compounds that were tested against several fungal and bacterial lineages, we have α-amirine (19), β-amirine (20), 17³-ethoxy-phaeophorbide A (104)¹⁰⁷ isolated from P. malacophylla, cycloart-23Z-en-3β,25-diol (28), 5,7-dihydroxy-3,8,4’-trimethoxyflavone (79)¹¹⁰ isolated from P. glazioviana, tiliroside (70)³¹,¹⁰⁷ isolated from P. malacophylla e P. distinguenda and caproic (10) and palmitic (3)¹⁰⁴ acids identified in P. odorata (Table 3).

Other activities

Other activities have been related for Pavonia species. Methanolic extract from P. odorata leaves has shown in vitro larvicide and repellent activities against Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus.¹⁵³ Researches have shown anti-hypertensive,³⁶,¹¹⁶,¹³² anti-helminthic,³⁵,¹⁴¹-¹⁴³,¹⁵² anti-urolithic,³⁴ gastroprotective,¹⁴⁹ laxative,¹³⁶ photoprotective,¹³¹ antiretroviral¹⁴⁶,¹⁴⁷ and several other kinds of activities.

Furthermore, a study on P. senegalensis has showed that fresh liquid ethanolic extract of leaves has not a very strong toxicity, becoming nephrotoxic and slightly hepatotoxic after 28 days.⁶⁸

CONCLUSIONS

Pavonia Cav. is one of the largest genus on Malvaceae sensu lato family and has showed different biologic activities amongst its species, which have already been mentioned in literature and scientific proved. Studies have shown that fatty acids, terpenoids, flavonoids and phenolics are the most common classes of secondary metabolites on this genus. Pharmacological in vivo, in vitro and in silico tests have given the researches promissory results due to the presence of those compounds, both isolated and present on the extracts, corroborating the reports of use of those herbs in folk medicine.

Nonetheless, there is a major need of keep exploring chemical and biological potentials of Pavonia species, both already and never studied, since medicinal plants are almost inexhaustible sources of bioactive molecules that can help the treatment and cure of several diseases that affect human populations worldwide.

This paper is a database with very relevant information from both phytochemical and biological studies of Pavonia species that can be further explored, aiming to understand the use of Pavonia by traditional medicine in various diseases, becoming alternatives for therapies by the use of these natural products with emphasis on the benefit of the world population.

ACKNOWLEDGMENTS

We thank Coordenação de Aperfeiçoamento do Ensino Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for all the support to our researches.

REFERENCES

• ¹
  Mohammed, F.; Shifa, S. P.; J. Pharmacogn. Phytochem. 2019, 8, 1887.
• ²
  Vijayashalini, P.; Jayanthi, G.; Abirami, P.; Journal of Medicinal Plants Studies 2017, 5, 331.
• ³
  Reddy, A. M.; Suresh Babu, M. V.; Rao, R. R.; Herba Pol., 2019; 65, 40 [Crossref].
• ⁴
  Sterlin Raj, T.; Edal Kuvin, J.; Asha, K. R. T.; Mohammed, A. A.; Puspharaj, A.; Raubbin, R. S.; World J. Pharm. Sci. 2016, 4, 518.
• ⁵
  Vadivel, V.; Sriram, S.; Brindha, P.; Int. J. Green Pharm. 2016, 10, 33 [Crossref].
• ⁶
  Fernandes, D. A.; Assis, E. B.; Souza, M. S. R.; Souza, P. I. V.; Souza, M. F. V.; Quim. Nova 2020, 43, 787 [Crossref].
• ⁷
  Johnson, M.; Maharajan, M.; Janakiraman, N.; Journal of Medicinal Herbs and Ethnomedicine 2015, 1, 125 [Crossref].
• ⁸
  Grings, M.; Boldrini, I. I.; Revista Brasileira de Biociências 2013, 11, 352.
• ⁹
  http://floradobrasil.jbrj.gov.br/jabot/floradobrasil/FB9118, acessada em abril 2022.
  » http://floradobrasil.jbrj.gov.br/jabot/floradobrasil/FB9118
• ¹⁰
  Esteves, G. L.; Krapovickas, A.; Boletim de Botânica da Universidade de São Paulo, 2009, 27, 63 [Crossref].
• ¹¹
  Mazzotti, M. R. R. M.; Dissertação de Mestrado, Universidade do Estado da Bahia, Brasil, 2015.
• ¹²
  Pando, A. M. S. C.; Dissertação de Mestrado, Instituto de Botânica da Secretaria do Meio Ambiente, Brasil, 2009.
• ¹³
  Behera, K. K.; Mandal, P.; Mahapatra, D.; Ethnobotanical Leaflets 2006, 10, 305.
• ¹⁴
  Madhu, V.; Naik, D. S. R.; Ethnobotanical Leaflets, 2009, 13, 1337.
• ¹⁵
  Mishra, R. K.; Patel, S. P.; Srivastava, A.; Vashistha, R. K.; Singh, A.; Puskar, A. K.; Nature and Science 2012; 10, 22.
• ¹⁶
  Singh, P. S.; Kumar, P. P.; Srinivasulu, D.; Nat. Oral Care Dent. Ther. 2020, 407 [Crossref].
• ¹⁷
  Kingston, C.; Nisha, B. S.; Kiruba, S.; Jeeva, S.; Ethnobotanical Leaflets 2007, 11, 32.
• ¹⁸
  Ranjithkumar, A.; Chittibabu, C. V.; Renu. G.; Indian Journal of Medicine and Healthcare 2014, 3, 322.
• ¹⁹
  Adebisi, I. M.; Alebiosu, O. C.; Int. J. Curr. Res. Chem. Pharm. Sci. 2014, 1, 81.
• ²⁰
  Tadesse, M.; Hunde, D.; Getachew, Y.; Ethiopian Journal of Health Sciences 2005, 15, 89.
• ²¹
  Megersa, M.; Jima, T. T.; Goro, K. K.; J. Evidence-Based Complementary Altern. Med. 2019, 1 [Crossref].
• ²²
  Babu, N. V. J.; Murty, P. P.; Rao, G. M. N.; International Journal of Botany and Research 2020, 10, 55.
• ²³
  Babu, N. V. J.; Murty, P. P.; Rao, G. M. N.; IOSR J. Pharm. Biol. Sci. 2020, 15, 44 [Crossref]
• ²⁴
  Kumar, R. B.; Suryanarayana, B.; Ethnobotanical Leaflets 2008, 12, 896.
• ²⁵
  Somashekhara Achar, K. G.; Boosanur, V.; Shivanna, M. B.; Indian Journal of Traditional Knowledge 2015, 1, 147.
• ²⁶
  Kannan, M.; Kumar, T. S.; Rao, M. V.; Global Journal Research Medicinal Plants & Indigenous Medicine 2016, 5, 203.
• ²⁷
  Tiwari, K. P.; Minocha, P. K.; Phytochemistry 1980, 19, 701 [Crossref].
• ²⁸
  Anand, R. M.; Nandakumar, N.; Karunakaran, L.; Ragunathan, M.; Murugan, V.; Natural Product Radiance 2005, 5, 139.
• ²⁹
  Daddam, J. R.; Kotha, P.; Katike, U.; Basha, S.; Dowlathabad, M. R.; Research Square 2020, 1 [Crossref].
• ³⁰
  Khare, C. P.; Indian Medicinal Plants - An Illustrated Dictionary, New Delhi, 2007.
• ³¹
  Agra, M. F.; Freitas, P. F.; Barbosa-Filho, J. M.; Rev. Bras. Farmacogn. 2007, 17, 114 [Crossref].
• ³²
  Garcia, C. M.; Tese de Doutorado, Universidade de Santa Maria, Brasil, 2007.
• ³³
  Caballero-George, C.; Gupta, M. P.; Planta Med. 2011, 77, 1189 [Crossref].
• ³⁴
  Ramprasad, R.; Anil, N.; Hameed, S. S.; Shifama, J. M. R.; Venkateshan, N.; J. Drug Delivery Ther. 2019, 9, 102 [Crossref].
• ³⁵
  Nakhare, S.; Garg, S. C.; Ancient Science of Life 1992, 12, 227.
• ³⁶
  Nakhare, S.; Garg, S. C.; Bhagwat, A. W.; Ancient Science of Life 1997, 17, 23.
• ³⁷
  Waghmare, S. D.; International Research Journal on Advanced Science Hub 2020, 2, 268 [Crossref].
• ³⁸
  Jamil, M.; Mansoor, M.; Latif, N.; Muhammad, S.; Gull, J.; Shoab, M.; Khan, A.; Pak. J. Sci. Ind. Res., Ser. B 2019, 62, 61 [Crossref].
• ³⁹
  Chitme, H. R.; Alok, S.; Jain, S. K.; Sabharwal, M.; Int. J. Pharm. Sci. Res., 2010, 1, 24 [Crossref].
• ⁴⁰
  Panda, S. P.; Sahoo, H. K.; Subudhi, H. N.; Sahu, A. K.; American Journal of Ethnomedicine 2014, 1, 260.
• ⁴¹
  Ahmed, S.; Hasan, M. M.; Ahmed, S. W.; Mahmood, Z. A.; Azhar, I.; Habtemariam, S.; Phytopharmacology 2013, 4, 390.
• ⁴²
  Ahmed, S.; Hasan, M. M.; Ahmed, S. W.; Pak. J. Pharm. Sci. 2014, 27, 1583.
• ⁴³
  Premamalini, P.; Sharmila, S.; International Journal of Advanced Herbal Science and Technology 2017, 3, 67 [Crossref].
• ⁴⁴
  Selvan, V. T.; Kakoti, B. B.; Gomathi, P.; Kumar, D. A.; Islam, A.; Gupta, M.; Mazumder, U. K.; Pharmacologyonline 2007, 2, 453.
• ⁴⁵
  Murty, P. P.; Rao, G. M. N.; Rao, D. S.; Journal of Science 2015, 5, 385.
• ⁴⁶
  Jenifer, S. P.; Lekha, K.; Journal of Medicinal Plants Studies 2019, 7, 196.
• ⁴⁷
  Shukla, V. S.; Nigam, I. C.; Proc. Inst. Chem. (India) 1961, 33, 229.
• ⁴⁸
  Baslas, K. K.; Perfum. Essent. Oil Rec 1959, 50, 896.
• ⁴⁹
  Kirtikar, K. R.; Basu, B. D.; Pâninî office, Bahadurganj, 1918.
• ⁵⁰
  Gritto, M. J.; Nanadagopalan, V.; Doss, A.; Adv. Appl. Sci. Res. 2015, 6, 157.
• ⁵¹
  Nandagopalan, V.; Doss, A.; Anand, S. P.; The International Journal Of Science & Technoledge 2014, 2, 1.
• ⁵²
  Bensy, D.; Gamble, A; Kaptchuk, T.; Chinese Herbal Medicine - Materia medica, 1993, 331.
• ⁵³
  Nayak, J. K.; Sahu, S. K.; Barik, E.; Bhattacharyay, D.; Pandey, M.; Plant Cell Biotechnol. Mol. Biol. 2020, 21, 166 [Crossref].
• ⁵⁴
  Lakshmanan, R.; Thiruvalluvar, M.; Subramanian, M. P. S.; Ganthi, A. S.; Eur. J. Biomed. Pharm. Sci. 2018, 5, 294.
• ⁵⁵
  Randive, K. R.; Hatekar, S.; Eastern Geographer 2010, 15, 79.
• ⁵⁶
  Sharma, J. P.; Srivastava, A.; Thakur, S. P.; Barpete, P. K.; Singh, S.; Int. J. Pharm. Life Sci. 2010, 1, 18.
• ⁵⁷
  Iswarya, P.; Lakshmikantham, T.; Mohan, S.; International Journal of Ayurveda and Pharma Research 2019, 7, 45.
• ⁵⁸
  Jayaprasad, B.; Thamayandhi, D.; Sharavanan, P. S.; International Journal of Research in Pharmaceutical and Biosciences 2012, 2, 1.
• ⁵⁹
  Deepthy, R.; Remashree, A. B.; International Journal of Herbal Medicine 2014, 2, 92.
• ⁶⁰
  Soudahmini, E.; Ganesh, M. S.; Panayappan, L.; Madhu, C. D.; Natural Product Radiance 2005, 4, 492.
• ⁶¹
  Shanmugam, S.; Annadurai, M.; Rajendran, K.; J. Appl. Pharm. Sci. 2011, 1, 94.
• ⁶²
  Karthiyayini, R.; Int. J. Pharm. Sci. Res. 2012, 3, 1829 [Crossref].
• ⁶³
  Manoranjitham, M.; Premalatha, S.; Int. J. Adv. Res. Biol. Sci., 2015, 2, 256.
• ⁶⁴
  Kumar, P. P.; Ayannar, M.; Ignacimuthu, S.; Indian Journal of Traditional Knowledge 2007, 6, 579.
• ⁶⁵
  Ticktin, T.; Dalle, S. P.; J. Ethnopharmacol., 2005, 96, 233. [10.1016/j.jep.2004.09.015]
  » https://doi.org/10.1016/j.jep.2004.09.015
• ⁶⁶
  Suryanarayana, S. N.; Seetharami, R. T. V. V.; Medicinal Plant Research 2017, 7, 1. [Crossref].
• ⁶⁷
  Andrade-Cetto, A.; Heinrich, M.; J. Ethnopharmacol. 2005, 99, 325. [Crossref].
• ⁶⁸
  Shehu, U. F.; Aliyu, I. M.; Ilyas, N.; Ibrahim, G.; Trop. J. Nat. Prod. Res. 2020, 4, 21. [Crossref].
• ⁶⁹
  Abdulhamid, Z.; Interviewer, Kaduna, 2016.
• ⁷⁰
  Neuwinger, H.; Medpharm Scientific, Stuttgart, 2000.
• ⁷¹
  Burkill, H. M.; Royal Botanic Gardens Kew, United Kingdom, 1997.
• ⁷²
  Francis, J. K.; Gen. Tech. Rep. IITF-GTR-26, San Juan, 2004.
• ⁷³
  Liogier, H. A.; Iberoamericana de Ediciones, Inc., San Juan, 1990.
• ⁷⁴
  Michael, M.; Dissertação de Mestrado, Universidade do Cairo, Egito, 2018.
• ⁷⁵
  Rasoanaivo, P.; Petitjean, A.; Ratsimamanga-Urverg, S.; Rakoto-Ratsimamanga, A.; J. Ethnopharmacol. 1992, 37, 117 [Crossref].
• ⁷⁶
  De Boer, H. J.; Kool, A.; Broberg, A.; Mziray, W. R.; Hedberg, I.; Levenfors, J. J.; J. Ethnopharmacol., 2005, 96, 461 [Crossref].
• ⁷⁷
  Dayal, B.; Purohit, R. M.; Flavour Industry 1971, 2, 484.
• ⁷⁸
  Rabearivony, A. D.; Kuhlman, A. R.; Razafiarison, Z. L.; Raharimalala, F.; Rakotoarivony, F.; Randrianarivony, T.; Rakotoarivelo, N.; Randrianasolo, A.; Bussmann, R. W.; Ethnobotany Research & Applications 2015, 14, 123 [Crossref].
• ⁷⁹
  Pavela, R.; Benelli, G.; Exp. Parasitol. 2016, 167, 103. [Crossref].
• ⁸⁰
  Karunamoorthi, K.; Hailu, T.; Journal of Ethnobiology and Ethnomedicine 2014, 10, 1 [Crossref].
• ⁸¹
  Degu, S.; Berihun, A.; Muluye, R.; Gemeda, H.; Debebe, E.; Amano, A.; Abebe, A.; Woldkidan, S.; Tadele, A.; Pharmacy & Pharmacology International Journal 2020, 8, 274 [Crossref].
• ⁸²
  Leal, R. S.; Maciel, M. A. M.; Dantas, T. N. C.; Melo, M. D.; Pissinate, K.; Echevarria, A.; Rev. Fitos 2007, 3, 26.
• ⁸³
  Mostardeiro, C. P.; Mostardeiro, M. A.; Morel, A. F.; Oliveira, R. M.; Machado, A. K.; Ledur, P.; Cadoná, F. C.; Silva, U. F.; Cruz, I. B. M.; Pharmacognosy Magazine 2014, 10, 630 [Crossref].
• ⁸⁴
  Grochowski, D. M.; Locatelli, M.; Granica, S.; Cacciagrano, F.; Tomczyk, M.; Compr. Rev. Food Sci. Food Saf. 2018, 17, 1395 [Crossref].
• ⁸⁵
  Samy, R. P.; Ignacimuthu, S.; J. Ethnopharmacol. 2000, 69, 63 [Crossref].
• ⁸⁶
  Kalarani, D. H.; Venkatesh, P.; Dinakar, A.; Res. J. Pharm. Technol. 2009, 2, 789.
• ⁸⁷
  Basu, S. K.; Rupeshkumar, M.; Kavitha, K.; Pharmacologyonline 2009, 1, 1144.
• ⁸⁸
  Kumari, A.; Lalitha, K. G.; Venkatachalam, T.; Kalaiselvi, P.; Sethuraman, M. G.; Asian Journal of Research in Pharmaceutical Science 2011, 1, 113.
• ⁸⁹
  Chavan, S.; Singh, A.; Daniel, M.; International Journal of Pharmaceutical Development & Technology 2014, 4, 157.
• ⁹⁰
  Kumar, M. P.; Sivasankar; Senthilvel, G.; Prabhu, L. R.; World J. Pharm. Pharm. Sci. 2018, 7, 644 [Crossref].
• ⁹¹
  Sathishkumar; Anbarasu; Int. J. Plant, Anim. Environ. Sci. 2019, 9, 6.
• ⁹²
  Bhuvaneswari, R.; Ramanathan, R.; Mathumathi, T. K.; Madheswaran, A.; Dhandapani, R.; Journal of Medicinal Plants Studies 2015, 3, 33.
• ⁹³
  Muthuraja, R.; Nandagopalan, V.; Thomas, B.; Marimuthu, C.; European Journal of Environmental Ecology 2014, 1, 33.
• ⁹⁴
  Murty, P. P.; Rao, G. M. N.; J. Phytol. 2010, 2, 17.
• ⁹⁵
  Madhava, C. K.; Sivaji, K.; Tulasi, R.; Students offset printers, Tirupati, 2008.
• ⁹⁶
  Wilson, E.; Rajamanickam, G. V.; Vyas, N.; Agarwal, A.; Dubey, G. P.; Indian Journal of Traditional Knowledge 2007, 6, 678.
• ⁹⁷
  Rao, D. M.; Rao, U. V. U. B.; Sudharshanam, G.; Ethnobotanical Leaflets 2006, 10, 198.
• ⁹⁸
  Madrigal, R. V.; Smith Jr., C. R.; Lipids 1973, 8, 407.
• ⁹⁹
  Bohannon, M. B.; Kleiman, R.; Lipids 1977, 13, 270.
• ¹⁰⁰
  Harwood, J. L. In The Biochemistry of Plants; Stumpf, P. K., ed.; Davis, 1980, cap. 1.
• ¹⁰¹
  Rao, K. S.; Lakshminarayana, G.; J. Am. Oil Chem. Soc. 1985, 62, 714.
• ¹⁰²
  Rayar, A.; Aeganathan, R.; Ilayaraja, S.; Prabakaran, K.; Manivannan, R.; Am. J. Phytomed. Clin. Ther. 2015, 3, 79.
• ¹⁰³
  Kumar, A.; Pande, C. S.; Kaul, R. K.; Indian J. Appl. Chem. 1965, 28, 190.
• ¹⁰⁴
  Dube, P.; Purohit, R. M.; Riechst., Aromen, Koerperpflegem. 1973, 23, 149.
• ¹⁰⁵
  Sahu, S. K.; Nayak, J. K.; Prakash, K. V. D.; Bhattacharyay, D.; Plant Cell Biotechnol. Mol. Biol. 2020, 21, 149.
• ¹⁰⁶
  Kashima, Y.; Nakaya, S.; Miyazawa, M.; J. Oleo Sci. 2014, 63, 149 [Crossref].
• ¹⁰⁷
  Chaves, O. S.; Tese de Doutorado, Universidade Federal da Paraíba, Brasil, 2016.
• ¹⁰⁸
  Albuquerque, J. B. L.; trabalho não publicado.
• ¹⁰⁹
  Lopes, L. G.; Dissertação de Mestrado, Universidade Federal do Espírito Santo, Brasil, 2014.
• ¹¹⁰
  Oliveira, M. S.; Tese de Doutorado, Universidade Federal da Paraíba, Brasil, 2019.
• ¹¹¹
  Casimiro-Júnior, F.; Chaves, O. S.; Fernandes, M. M. M. S.; Agra, M. F.; Teles, Y. C. F.; Souza, M. F. V.; 36ª Reunião Anual da Sociedade Brasileira de Química, São Paulo, Brasil, 2013.
• ¹¹²
  Fernandes, M. M. M. S.; Dissertação de Mestrado, Universidade Federal da Paraíba, Brasil, 2013.
• ¹¹³
  Gualberto, F. T. A.; Trabalho de Conclusão de Curso, Universidade Federal da Paraíba, Brasil, 2013.
• ¹¹⁴
  Fernando, L. M.; Lima, A. A.; Dias, W. S.; Moura-Júnior, R. T.; Teles, Y. C. F.; Souza, M. F. V. In Processos Químicos e Biotecnológicos; Andrade, D. F., Souza, A. A., Andrade, D. E., Oliveira, E. J., Santos, F., Lopes, J. E. F., Neves, O. F.,Lima, L. C., Ferreira Filho, N., Oliveira, V. A., eds.; Editora Poisson: Belo Horizonte, 2020, cap. 3.
• ¹¹⁵
  Puckhaber, L. S.; Stipanovic, R. D.; Bost, G. A.; Herbs, Medicinals, and Aromatics 2002, 556.
• ¹¹⁶
  Andrade, T. U.; Ewald, B. T.; Freitas, P. R.; Lenz, D.; Endringer, D. C.; Int. J. Pharm. Pharm. Sci. 2012, 4, 124.
• ¹¹⁷
  Silva, C. M.; Trabalho de Conclusão de Curso, Universidade Federal da Paraíba, Brasil, 2018.
• ¹¹⁸
  Sotelo, A.; Villavicencio, H.; Montalvo, I.; Gonzalez-Garza, M. T.; Afr. J. Tradit., Complementary Altern. Med. 2005, 1, 4 [Crossref].
• ¹¹⁹
  Gasca, C. A.; Cabezas, F. A.; Torras, L.; Bastida, J.; Codina, C.; Free Radicals and Antioxidants, 2013, 3, 55 [Crossref].
• ¹²⁰
  Tiwari, K. P.; Minocha, P. K.; Masood, M., Proc. Natl. Acad. Sci., India, Sect. A 1978, 48, 158.
• ¹²¹
  Tiwari, K. P.; Choudhary, R. N.; Acta Cienc. Indica, Chem. 1980, 6, 36.
• ¹²²
  Desbois, A. P.; Smith, V. J.; Appl. Microbiol. Biotechnol., 2010, 85, 1629 [Crossref].
• ¹²³
  Mandey, J. S.; Wolayan, F. R.; Pontoh, C. J.; Kowel, Y. H. S.; Scientific Papers, Series D, Animal Science 2020, 63, 214.
• ¹²⁴
  Seidel, V.; Taylor, P. W.; Int. J. Antimicrob. Agents 2004, 23, 613 [Crossref].
• ¹²⁵
  Fernandes, D. A.; Chaves, O. S.; Teles, Y. C. F.; Agra, M. F.; Vieira, M. A. R.; Silva, P. S. S.; Marques, M. O. M.; Souza, M. F. V.; Quim. Nova 2021, 44, 137 [Crossref].
• ¹²⁶
  Yadav, N.; Yadav, R.; Goyal, A.; Int. J. Pharm. Sci. Rev. Res. 2014, 27, 272.
• ¹²⁷
  Lopes, L. G.; Tavares, G. L.; Thomaz, L. D.; Sabino, J. R.; Borges, K. B.; Vieira, P. C.; Veiga, T. A. M.; Borges, W. S.; Chem. Biodiversity 2016, 13, 284 [Crossref].
• ¹²⁸
  Santos, R. A. F.; Dissertação de Mestrado, Universidade Federal da Bahia, Brasil, 2010.
• ¹²⁹
  Santos, D. S.; Rodrigues, M. M. F.; Estação Científica (UNIFAP) 2017, 7, 29 [Crossref].
• ¹³⁰
  Sousa, A. P.; Oliveira, M. S.; Fernandes, D. A.; Ferreira, M. D. L.; Cordeiro, L. V.; Souza, H. D. S.; Souza, M. F. V.; Pessoa, H. L. F.; Oliveira-Filho, A. A.; Silveira e Sá, R. C.; Scientific Electronic Archives 2021, 13, 120 [Crossref].
• ¹³¹
  Sousa, A. P.; Nunes, M. K. S.; Oliveira, M. S.; Fernandes, D. A.; Ferreira, M. D. L.; Cordeiro, L. V.; Souza, H. D. S.; Souza, M. F. V.; Pessoa, H. L. F.; Oliveira Filho, A. A.; Silveira e Sá, R. C.; Sci. Plena 2020, 16, 1 [Crossref].
• ¹³²
  Silva, G. C.; Pereira, A. C.; Rezende, B. A.; Silva, J. F. P.; Cruz, J. S.; Souza, M. F. V.; Gomes, R. A.; Teles, Y. C. F.; Cortes, S. F.; Lemos, V. S.; Planta Med. 2013, 79, 1003. [Crossref].
• ¹³³
  Rajalakshmi, P.; Vadivel, V.; Subashini, G.; Pugalenthi, M.; Int. J. Adv. Res. 2016, 4, 1751 [Crossref].
• ¹³⁴
  Silva, C. M.; Félix, M. D.; Aquino, A. K.; Oliveira, M. S.; Teles, Y. C. F.; Souza, M. F. V.; Mol2Net 2016, 2, 1 [Crossref].
• ¹³⁵
  Badami, S.; Channabasavaraj, K. P.; Pharm. Biol. 2007, 45, 392 [Crossref].
• ¹³⁶
  Kalarani, D. H.; Dinakar, A.; Senthilkumar, N.; Int. J. Drug Dev. Res. 2012, 4, 298.
• ¹³⁷
  Kirtikar, K. R.; Basu, B. D.; Indian Medicinal Plants, International Book Distributors Book Sellers and Publishers: Deheradun, 1999.
• ¹³⁸
  Girish, H. V.; Vinod, A. B.; Dhananjaya, B. L. Satish Kumar, D.; Duraisamy, S.; Pharmacogn. J. 2016, 8, 28 [Crossref].
• ¹³⁹
  Rayar, A.; Manivannan, R.; Int. J. Pharm. Sci. Invent. 2015, 4, 46 [Crossref].
• ¹⁴⁰
  Lozano, C. M.; Vasquez-Tineo, M. A.; Ramirez, M.; Infante, M. I.; Pharmacogn. Commun. 2021, 11, 52 [Crossref].
• ¹⁴¹
  Garg, S. C.; Anthelmintic activity of some medicinal plant products, Research Periodicals and Book Publishing House, Houston, 2003, 207.
• ¹⁴²
  Garg, S. C.; Natural Product Radiance 2005, 4, 18.
• ¹⁴³
  Bhavani, S.; J. Pharm. Sci. Res. 2015, 7, 812.
• ¹⁴⁴
  Singh, D.; Singh, B.; Dutta, B. K.; International Journal of Science 2012, 4, 3 [Crossref].
• ¹⁴⁵
  Mapunya, M. B.; Dissertação de Mestrado, Universidade de Pretória, África do Sul, 2009.
• ¹⁴⁶
  Matsuse, I. T.; Lim, Y. A.; Hattori, M.; Correa, M.; Gupta, M. P.; J. Ethnopharmacol. 1999, 64, 15 [Crossref].
• ¹⁴⁷
  Dan, G.; Castellar, A.; Alumni - Revista Discente da UNIABEU 2015, 3, 8.
• ¹⁴⁸
  Shaku, M.; Yamamoto, T.; Shishido, M.; Takashi, T.; Yoshitani, S.; Yoshimi, F., Jpn. Kokai Tokkyo Koho 2001 (JP 2001181172).
• ¹⁴⁹
  Ewald, B. T.; Loyolla, C. M.; Pereira, A. C. H.; Lenz, D.; Medeiros, A. R. S; Andrade, T. U.; Nogueira, B. V.; Pereira, T. M. C.; Endringer, D. C.; Rev. Bras. Plantas Med. 2015, 17, 392 [Crossref].
• ¹⁵⁰
  Vahitha, R.; Venkatachalam, M. R.; Murugan, K.; Jebanesan, A.; Bioresour. Technol. 2002, 82, 2 [Crossref].
• ¹⁵¹
  Kamaraj, C.; Abdul Rahuman, A.; Bagavan, A.; Abduz Zahir, A.; Elango, G.; Kandan, P.; Rajakumar, G.; Marimuthu, S.; Santhoshkumar, T.; Tropical Biomedicine 2010, 27, 211.
• ¹⁵²
  Singhai, A.; Singour, P. K.; Garg, G.; Pawar, R. S.; Patil, U. K.; Research Journal of Pharmacology and Pharmacodynamics 2009, 1, 82.
• ¹⁵³
  Selvakumar, B.; Gokulakrishnan, J.; Elanchezhiyan, K.; Deepa, J.; International Journal of Current Advanced Research 2015, 4, 221.
• ¹⁵⁴
  Mago, N.; Sofat, I. B.; Jethi, R. K.; Indian J. Med. Res. 1989, 90, 77.
• ¹⁵⁵
  Jethi, R. K.; Duggal, B.; Sahota, R. S.; Gupta, M.; Sofat, I. B.; Indian J. Med. Res. 1983, 78, 422.
• ¹⁵⁶
  Jeeva Gladys, R.; Kalai Arasi, R.; Elangovan, S.; Mubarak, H.; J. Appl. Pharm. Sci. 2013, 3, 176 [Crossref].

Publication Dates

• Publication in this collection
  28 Oct 2022
• Date of issue
  2022

History

• Received
  17 Dec 2021
• Accepted
  17 Mar 2022
• Published
  19 Apr 2022